1. Field of the Invention
This invention is directed to novel cross-linked vancomycin-cephalosporin compounds which are useful as antibiotics. This invention is also directed to pharmaceutical compositions comprising such compounds; methods of using such compounds as antibacterial agents; and processes and intermediates for preparing such compounds.
2. State of the Art
Various classes of antibiotic compounds are known in the art including, for example, β-lactam antibiotics, such as cephalosporins, and glycopeptide antibiotics, such as vancomycin. Cross-linked antibiotic compounds are also known in the art. See, for example, U.S. Pat. No. 5,693,791, issued to W. L. Truett and entitled “Antibiotics and Process for Preparation”; WO 99/64049 A1, published on Dec. 16, 1999, and entitled “Novel Antibacterial Agents”. Additionally, WO 03/031449 A2, published on Apr. 17, 2003, and entitled “Cross-Linked Glycopeptide-Cephalosporin Antibiotics” discloses compounds having a glycopeptide group covalently linked to the oxime moiety of a cephalosporin group.
Due to the potential for bacteria to develop resistance to antibiotics, however, a need exists for new antibiotics having unique chemical structures. Additionally, a need exists for novel antibiotics having improved antibacterial properties including, by way of example, increased potency against Gram-positive bacteria. In particular, a need exists for new antibiotics that are highly effective against antibiotic-resistant strains of bacteria, such as methicillin-resistant Staphylococci aureus (MRSA).